Multi-Scale Modeling of Central Nervous System White Matter

本研究的主要目标是开发一种基于代表性体积元素的多尺度建模方法，以实现对中枢神经系统(CNS)白质的准确描述和有限元分析，特别是脑和脊髓损伤。做到这一点的工具是一种综合的多学科分析、计算和实验方法，由几个同样重要的步骤组成。该项目的基本假设是，在脊髓损伤期间，轴突纤维既没有牢牢地拴在神经胶质基质上，也没有完全脱离；事实上，随着拉伸的增加，它们会变得更紧密。为此，需要结合当前研究忽略的微观运动学来准确地表示大脑和脊髓的白质并对其进行建模。在这个项目的过程中，我们将开发一种新的中枢神经系统白质材料模型，该模型将在宏观尺度连续分析中捕捉轴突的微观尺度行为。该模型的开发将通过新颖的现场实验来指导和检验。所提出的工作的主要智力优点在于将微结构轴突和神经胶质的特征和属性计算并入中枢神经系统白质的全局(宏观)响应中，以及在各种加载场景下对模拟数据进行现场实验关联和验证。这项研究的结果将引领轴突损伤耐受性标准的制定，这一标准至关重要，因为轴突损伤是颅脑损伤和脊髓损伤后功能丧失的近端原因。它还将帮助设计新的体内和体外模型，目的是在电子计算机预测的基础上，在特定的模式和位置诱导损伤。社会影响在于，完成后，中枢神经系统白质模型将能够整合到具有更复杂载荷条件的脊髓损伤和脑外伤的分析中，以预测单个轴突水平的损伤。这是中枢神经系统生物力学建模的一项突破，它可以极大地促进诊断，最终导致改进损伤第一反应和治疗的手段和措施。这个项目在基础研究和知识传播方面的影响是显而易见的，因为这个多学科项目引入了材料科学、生物工程、控制和高科技计算技术的任务，以开发具有独特定量测量能力的最先进的组织诊断模型，并对其进行全面的数学描述。这对我们的研究生不仅在科学和工程领域，而且在指导和推广方面都将产生重大的教育影响，因为他们是我们通过罗格斯未来学者计划所做的社区努力的一部分。积极招收少数民族及代表以下群体的研究生和本科生。这些计划为这些学生提供了独特的机会，这些机会将使他们对工程方面的教育和培训感到兴奋，并有助于塑造我们科学和工程界未来的领导者。最后，为支持成果传播和外展，私营部门已获得资金，用于参加CMMI每两年举行一次的受赠人会议。

The primary objective of this research is to develop a mutli-scale modeling approach based on representative volume elements to enable the accurate depiction and finite element analysis of central nervous system (CNS) white matter, in particular of brain and spinal cord trauma. The vehicle to do this is an integrated multi-disciplinary analytical, computational and experimental methodology consisting of several equally important steps. The underlying hypothesis for the project is that axon fibers are neither firmly tethered nor completely uncoupled to the glial matrix during spinal cord trauma; in fact, they become more tethered with increasing stretch. To this end, microstructural kinematics, omitted by current studies, need to be incorporated to accurately represent and model the white matter of the brain and spinal cord. During the course of this project, we will develop a novel material model for CNS white matter that will capture the micro-scale behavior of axons in a macro-scale continuum analysis. The development of this model will be guided and tested by novel in situ experiments. The major intellectual merit of the proposed work lies upon the computational incorporation of the microstructural axon and glial features and properties into the global (macro) response of the CNS white mater, and the in situ experimental correlation and validation of the simulation data for a variety of loading scenarios. Results from this research will spearhead the development of axon damage tolerance criteria, which is of paramount importance since injury to axons is the proximal cause for loss of function following TBI and SCI. It will also assist in designing new in vivo and in vitro models with the goal of inducing injury in specific patterns and locations based on in silico predictions.The societal impact lies in that, upon completion, the CNS white mater model will be able to be integrated into analyses of SCI and TBI with more complex loading conditions to predict injury at the single axon level. This is a breakthrough in the CNS biomechanical modeling, which can greatly facilitate diagnostics that can ultimately lead to improved means and measures of injury first response and treatment. The impact of this project in terms of basic research and the spread of knowledge is evident since this multidisciplinary program brings in tasks from materials science, bioengineering, controls, and hi-tech computational techniques, to develop a state of the art tissue diagnostic model, with unique quantitative measuring capabilities and that is described mathematically to its entirety. The educational impact will be significant for our graduate students not only in scientific and engineering fields, but also in mentoring and outreach since they are an integral part of our community efforts through the Rutgers Future Scholars program. Graduate students and undergraduates from minority and under represent groups will be actively recruited. These initiatives provide unique opportunities to these students that will excite them about education and training in engineering and help shape future leaders of our scientific and engineering communities. Finally, in support of results dissemination and outreach, the PI has secured funding to attend the CMMI bi-annual grantees' meeting.